Submissions for variant NM_031935.3(HMCN1):c.9182A>G (p.His3061Arg)

gnomAD frequency: 0.00001  dbSNP: rs748058327

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000331636	SCV000351894	uncertain significance	Age related macular degeneration 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001850506	SCV002202791	uncertain significance	not provided	2023-01-20	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs748058327, gnomAD 0.02%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 294208). This variant has not been reported in the literature in individuals affected with HMCN1-related conditions. This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 3061 of the HMCN1 protein (p.His3061Arg).
CeGaT Center for Human Genetics Tuebingen	RCV001850506	SCV004009906	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	HMCN1: BP4